美国纽约大学Jayeeta Basu研究小组取得一项新突破。他们研究出海马体通过直接反馈回路塑造内嗅皮层输出。2025年2月18日，国际知名学术期刊《自然—神经科学》发表了这一成果。

与内嗅皮层到海马体的通路不同，课题组对海马体到皮层反馈回路的组织和功能知之甚少。

在小鼠中，研究组报告了两个功能不同的平行海马-内嗅皮质反馈通路：通过第5层的典型失联通路和通过第2/3层的新颖单突触输入通路。电路映射显示，海马输入主要驱动第5层的兴奋，而在第2/3层的前馈抑制。当与皮层第1层输入重复配对时，海马输入在第5层进行同突触增强，但在第2/3层诱导异突触可塑性和尖峰输出。在行为上，海马体对第5层和第2/3层的输入分别支持对象记忆编码和它们的回忆。导航过程中的双光子成像显示海马抑制减少了空间调谐的皮层轴突活动。研究组提出了一个模型，海马体反馈可以迭代地塑造正在进行的皮层处理。

据介绍，他们的大脑将感觉、认知和内部状态信息与记忆整合，以提取行为相关性。皮质-海马体的相互作用可能介导了这种相互作用，但潜在的电路机制仍然是未知的。

附：英文原文

Title: Hippocampus shapes entorhinal cortical output through a direct feedback circuit

Author: Butola, Tanvi, Hernndez-Frausto, Melissa, Blankvoort, Stefan, Flatset, Marcus Sandbukt, Peng, Lulu, Hairston, Ariel, Johnson, Cara Deanne, Elmaleh, Margot, Amilcar, Amanda, Hussain, Fabliha, Clopath, Claudia, Kentros, Clifford, Basu, Jayeeta

Issue&Volume: 2025-02-18

Abstract: Our brains integrate sensory, cognitive and internal state information with memories to extract behavioral relevance. Cortico–hippocampal interactions likely mediate this interplay, but underlying circuit mechanisms remain elusive. Unlike the entorhinal cortex-to-hippocampus pathway, we know little about the organization and function of the hippocampus-to-cortex feedback circuit. Here we report in mice, two functionally distinct parallel hippocampus-to-entorhinal cortex feedback pathways: the canonical disynaptic route via layer 5 and a novel monosynaptic input to layer 2/3. Circuit mapping reveals that hippocampal input predominantly drives excitation in layer 5 but feed-forward inhibition in layer 2/3. Upon repetitive pairing with cortical layer 1 inputs, hippocampal inputs undergo homosynaptic potentiation in layer 5, but induce heterosynaptic plasticity and spike output in layer 2/3. Behaviorally, hippocampal inputs to layer 5 and layer 2/3 support object memory encoding versus recall, respectively. Two-photon imaging during navigation reveals hippocampal suppression reduces spatially tuned cortical axonal activity. We present a model, where hippocampal feedback could iteratively shape ongoing cortical processing.

DOI: 10.1038/s41593-025-01883-9

Source: https://www.nature.com/articles/s41593-025-01883-9